The long-range objective of this research project is to better understand how mitochondrial ATPase participates in the process of ATP synthesis and in the process of ATP utilization in both normal and neoplastic cells. Special emphasis is being given to molecular studies of the ATPase complex of normal cells is an attempt to elucidate the mechanisms of ATP synthesis and ATP utilization, and to understand how these two processes are regulated. Emphasis is being given also to molecular studies of the ATPase complex of neoplastic cells in order to ascertain whether ATP synthesis or ATP utilization, or the regulation of these two activities has been altered in any way during transformation. To meet these objectives we are studying the structural and catalytic properties of the oligomycin-sensitive ATPase of normal and neoplastic tissue and three of its functional components: F1, the ATP hydrolytic unit; Fo, the oligomycin-sensitivity conferring unit; and l, a small peptide inhibitor of the ATPase. For these studies we use mitochondria from rat liver because much is known about the mitochondrial inner membrane from this tissue (Chan, Greenawalt, and Pederson, J. Cell Biol. 45, 291, 1970); because we have purified the olgomycin-sensitive ATPase complex and its F1 component from this tissue (Soper and Pederson, Biochem., In Press, 1975; Catterall and Pederson, J. Biol. Chem. 246, 4987, 1971); and because we have shown that many hepatoma mitochondria are defective in their capacity to hydrolyze ATP in the presence of an uncoupling agent (Pederson and Morris, J. Biol. Chem. 249, 3327, 1974). The research currently being conducted in this laboratory is very necessary and fundamental to a complete understanding of energy coupling and utilization in both normal and transformed cells. BIBLIOGRAPHIC REFERENCES: 1. Pedersen, P. L., ATP-Dependent Reactions Catalyzed By Inner Membrane Vesicles of Rat Liver Mitochondria-Kinetics, Substrate Specificity, and Bicarbonate Sensity. J. Biol. Chem., 251, 934 (1976). 2. Pedersen, P. L., Interaction of Homogeneous Mitochondrial ATPase From Rat Liver With Adenine Nucleotides and Inorganic Phosphate. J. of Supramolecular Structure, 3, 222 (1975).